Scientists optimise delivery of mRNA to target cells

Monash University researchers claim to have developed a simple yet highly effective method for delivering mRNA to target cells, opening up new possibilities for future non-vaccine mRNA medicines for a broad range of diseases.

Led by the Monash Institute of Pharmaceutical Sciences (MIPS), the interdisciplinary team of researchers used advanced technologies coupled with preclinical studies to produce a highly versatile method that captures and attaches antibodies to the surface of mRNA-loaded lipid nanoparticles while the antibodies are in their optimal orientation, thus enhancing the mRNA’s effectiveness and reducing side effects by making sure it only reaches its target destination. Their work has been published in the journal Nature Nanotechnology.

Lipid nanoparticles are tiny, spherical particles made of lipids (fatty compounds) used to deliver drugs. They are an emerging technology for gene delivery and a key component of mRNA medicines as they help protect the mRNA cargo from being broken down or cleared by the body before it can reach the target cell.

“In mRNA medicine, it’s not just about what we deliver — it’s about where and how we deliver it,” noted MIPS PhD candidate Moore Zhe Chen, co-lead author on the study. “Our findings show the precise orientation of targeting ligands on lipid nanoparticles plays a vital role in ensuring that mRNA reaches the right cells with maximum efficiency. This level of control opens up new possibilities for developing mRNA medicines with far greater specificity.”

Drug delivery expert and co-lead author Associate Professor Angus Johnston, also from MIPS, added that efficient and precise delivery of mRNA is critical to advance mRNA medicines beyond their current use as vaccines.

“In 2021 the world was introduced to the first mRNA-lipid nanoparticle vaccines to combat the COVID-19 pandemic, demonstrating the exciting potential of lipid nanoparticles to effectively deliver mRNA to cells,” Johnston said. “However, current delivery techniques require modification of antibodies, which can dilute their efficacy and doesn’t translate well to non-vaccine mRNA medicines.

“In this study we used powerful imaging techniques to develop a simple antibody capture system that requires no modification of the antibody, and ensures the antibodies are attached onto lipid nanoparticles in an orientation that increases binding to target cells. This is vital for developing new mRNA medicines beyond vaccines.”

The MIPS method has already increased the binding of mRNA to target cells eight-fold compared to conventional antibody capture methods. The research team confirmed the efficacy of the method in preclinical studies, which demonstrated the efficient delivery of mRNA to T cells (white blood cells that play a vital role in the immune system) in mice, resulting in limited off-target delivery to other immune cells.

The MIPS team is now working to harness their platform to tackle a range of diseases that are difficult to treat with conventional drugs. By enabling precise delivery of mRNA to specific cell types, the technology holds promise for advancing treatments in cancer, genetic disorders and autoimmune disease, where targeted therapies could dramatically improve outcomes by enabling cells to produce therapeutic proteins exactly where they are needed.

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